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Phenol may be condensed with a -keto ester(ethyl

acetoacetate) under the influence of sulphuric acid (Von

pechmann reaction ) thus resorcinol readily under goes this

condensation to give

7-hydroxy-4-methyl Coumarin . A coumarinic ester can be anintermediate in this synthesis.

OH OH

+CH

2

C2H5OCO

CO

CH3

H2SO4

Conc.

OH OH

H

CH

C2H5OCO

COH

CH3

- H2O

OH OH

CHC

CH3

- C2H5OH

+ H2O

OH OH

CHC

CH3

CO

OH

OH OC

CHC

O

CH3

- H2

O

Resorcinol Ethylacetoacetate

Coumarinic ester

7-hydroxy-4-methylcoumarin

C O

OC2H5

1

Preparation of 7-hydroxy-4-methylCoumarin

Lab

1

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Required:

#Resorcinol 5.5 gm.

#Ethyl acetoacetate 6.5 gm 6.4 ml.

Conc. H2SO4 50 ml# .

Procedure:

1-In 100 ml conical flask put 5.5 gm of resorcinol (0.05M )and 6.4 ml of ethyl acetoacetate then add 50 ml of H2SO4

to conical flask.

2-Heat a mixture on the water bath for 30 minutes.

3-Cool the resulting solution and stir into crushed ice 250 gm.

4-Filter the product and wash with 100 ml H2O then weight

this product.

5-Crystallization of the coumarin carried out by methanol and

then measure m.p. .

2

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OH O O

CH3

7-hydroxy-4-methylcoumarin

CH3I

K2CO3

O O O

CH3

7-methoxy-4-methylcoumarin

H3C

Required:

#K2CO3 2 gm.

#Acetone 10 ml.

#Coumarin 1.76 gm.

#CH3I 2ml.

Procedure:

1-In dry round bottom flask (50 ml) put 2gm of potassium

carbonate K2CO3 (anhydrous) then add 1.76gm of Coumarin

witch dissolved in 10 ml of acetone.

2-The mixture was treated with 2ml of methyl iodide CH3I.

3-The reaction was refluxed on water bath for 2 hour.

4-Cool the resulting solution and stir into crushed ice 250 gm.

5-After the reaction was completed filter the product and wash

with 100ml water.

6-Crystallization the product carried out by methanol and

then measure m.p.

3 talytecAiramuoC

talyhteMiramuoC

baL

2

baL2

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Required:

#Coumarin 1.76 gm.#Pyridine 5 ml.

#AC2O 2 ml.

Procedure:

1-In dry round bottom flask (50ml) add 1.76gm of Coumarin

was dissolved in 5 ml of pyridine then treated withacetic anhydride AC2O 2 ml.

2-The reaction was refluxed on water bath for 2 hour.

3-Cool the resulting solution and stir into crushed ice 250 gm.

4-After the reaction was completed filter the product and wash

with 100ml water.5-Crystallization the product carried out by methanol and

then measure m.p. .

OH O

CH3

O

7-hydroxy-4-methylcoumarin

C6H5C-C

pyridine

O O O

CH3

7-benzoyl-4-methylcoumarin

OC

Ph

O

Required:

4

neB

uoC

baL

2

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#Coumarin 1.76gm.

#pyridine 5ml.

#benzoyl chloride 5ml.

Procedure:

1-In dry round bottom flask (50ml) add 1.76gm of Coumarin

was dissolved in 5 ml of pyridine then add 5 ml of benzoyl

chloride.

2-The reaction was refluxed on water bath for 2 hour.

3-Cool the resulting solution and stir into crushed ice 250 gm.

4-After the reaction was completed filter the product and wash

with100ml water.

5-Crystallization the product carried out by methanol and

then measure m.p. .

Pyrazoles are readily prepared by the action of hydrazine or

substituted hydrazines on 1,3-diketones. The reaction proceeds

via ring closure of the initially formed hydrazone . Interaction

of acetylacetone with hydrazine hydrate leads to 3,5-dimethyl

pyrazole.

5

Preparation of 3,5-Dimetyl pyrazole

Lab

3

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Required:

#acetophenone 5.6 ml.

#phenyl hydrazine 5 ml.

Procedure:

1-In 50 ml round bottomed flask, place acetophenone 5.6 ml

and distilled phenyl hydrazine 5ml.

2-Heat the mixture on water bath at 100 for 1hour then cool

and stir until the reaction mixture solidifies.

3-Stir with 10 ml ethanol, then filter the product and wash

with ice-cold 10ml ethanol.

8

+CPh Me

O NH

N

NH

NH2

C

CH3

P

NNH

C

H2

Ph+ H

+

NH

NH2

C

CH2

Ph+

PPA

N

CH2

H

C Ph

+

NH2

+

N

CH2

HNH

2

Ph- NH3

N Ph

phenyl hydrazine acetophenone acetophenonephenylhydrazone

2-phenylindole

- H+

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4-acetophenone Phenylhydrazone is obtained as yellow

product then measure m.p. .

Procedure:

1-In conical flask add 5gm of acetophenone

phenylhydrazone

with 30ml phosphoric acid and stir the mixture at 100

For 1 hour on water bath.

2-Cool the solution, stir into ice-water 250gm and filter the

grey precipitate then wash with 100 ml cold H2O.

9

Preparation of 2- Phenyl indole

baL

5

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3-Crystallization the product carried out by ethanol and then

measure m.p. .

The

phe

nyl-hydrazone derivatives of acyclic Ketones are readily

cyclized to indoles in the presence of zink Chloride.

}Fiscer indole synthesis }. Borsche showed that the phenyl-

hydrazone cyclohexanone undergoes a similar reaction to yield

1,2,3,4-tetrahydrocarbazole . Glacial acetic acid is used in this

case as the solvent for phenyl-hydrazone formation and also as

the cyclizing agent.

10

Preparation of 1,2,3,4-Tetrahydrocarbazole

baL

6

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Required:

#cyclohexanone (4.75gm; 5ml. (

#phenyl hydrazine ( 5.4gm; 4.5ml.(

#glacial acetic acid 30ml.

Procedure:

1-In 100ml round bottomed flask, add cyclohexanone 5ml in

glacial acetic acid 30ml and 4.5ml of phenyl hydrazine.

2-Heat the mixture under reflux for 10 minutes then cool

and filter the brown product and wash with100ml cold

H2O.

3-Crystallization the product carried out by 50% aqueous

ethanol and then measure m.p. .

11

Note

NH

NH

H

phenyl hydrazine cyclohexanon

+

-

O

+N N H

OH

H - H2O

N N H

H

+ H+

N NH2

H+

AcOH

NNH

2

H

+

+

N

HNH

2

H

N

H

- NH3- H

1

2

3

4

1,2,3,4-tetrah dro carbazol

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Tetrahydro carbazole must not be dried in an oven , since it is

readily oxidized to the hydroperoxide.

Benzil , hexamine and ammonium acetate react in acetic acid to

yield 4,5 diphenyl imidazole.

12

Preparation of 4,5- Diphenylimidazole

+6H2O 6CH2O + 4NH3

N

CH2

N

N

CH2

N

CH2

Hexamine

baL

7

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Required:

benzil 2.1gm . # hexamine 0.26gm# .

ammonium acetate 6 gm . #glacial acetic acid 50ml# .

Procedure:

1-In 100ml round bottomed flask, heat a solution of 2.1 gmbenzil , 0.26 gm of hexamine and ammonium acetate 6 gm

in glacial acetic acid 50ml under reflux for 1 hour.

2-Add the resulting solution to 400ml water and remove any

turbidity that may develop followed by adding small amount

of carbon and then filtration.

3-precipitate the product by concentrated with 70ml NH4OH

13

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with cooling , then filter and wash with 50ml H2O.

4-Crystallization the product carried out by 10ml pyridine

and 10ml hot H2O then measure m.p. .

5-isoxazolones are prepared by the action of hydroxylamine

hydrochloride on -keto esters. Initial reaction of the

hydroxylamine with the ketone group yield an oxime which

then cyclizes to the 5-isoxazolones . Interaction of ethyl

benzoyl - acetate with hydroxylamine hydrochloride yield 3-

phenyl-

5-isoxazolone .

14

Preparation of 3-phenyl-5-isoxazolone

baL

8

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Required:

#ethyl benzoyl acetate ( 9.6gm ; 8.5ml. (

#hydroxylamine hydrochloride 3.5gm.

#ethanol 20ml.

Procedure:

1-In 100ml round bottomed flask, add a solution of 8.5ml ethyl

benzoyl acetate in 30ml ethanol and 3.5gm hydroxylamine

hydrochloride NH2OH.HCl, 5gm sodium acetate in 12ml

H2O.

2-Heat the mixture under reflux for 2 hour then allow to cool

and filter the product.

3-Crystallization the product carried out by ethanol and

15

CH2

C

OEt

Cph

O

+HNHOH CH2

CO

OEt

C ph

NHOH

OH

CH2

C

OH

Cph

NOH+H2O

-EtOH

CH2

CO

OEt

Cph

NOH

-H2O

-H2O

CH2

CO

Cph

N

O

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then measure m.p. .

Condensation of ethyl acetoacetate and it's derivatives with

various phenyl-hydrazines gives rise to the corresponding

phenyl-hydrazones , which yield pyrazolones on cyclization .Interaction of ethyl acetoacetate and phenyl-hydrazine lead

directly to 3-Methyl-1-Phenyl-5-Pyrazolone .

16

erPzaryP

CH2C

O

CH3

C

+HHN

NH

CH2C

O

H3C

CHO

HN

baL

9

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Required:

#ethyl acetoacetate (6.5gm ; 6.35 ml. (

#phenyl-hydrazine(4.4gm ; 4.9 ml. (

Procedure:

1-In 100ml round bottomed flask, heat a mixture of 6.35ml

ethyl acetoacetate and distilled 4.9ml of phenyl-hydrazine at

120

on oil bath for 1 hour.

2-Cool the resulting red oil and stir with 50ml ether until

solidification occurs , then filter the product and wash

with 20ml ether.

3-Crystallization the product carried out by 50% aqueous

ethanol and then measure m.p. .

17

EtO phOEt

NH

ph

CH2C

N

N

C

CH3

h

O

-H2OCH2C

N

NH

C

ph

OHO

-H2O

+H2O

CH3

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Diazotization of -phenylene diamine in dilute acid solution

yields benzo-triazole . The reaction proceeds via the mono-

diazonium salt , which then couples with the adjacent amino

-group to give the internal diazoamino compound ,

benzotriazole.

18

Preparation of Benzotriazole

NH2

NH2

NHO2

AcOH

N2

NH2

N

NN

|H

Lab1

0

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References:

Practical heterocyclic Chemistry by: F:Tion Smalley#.

#A text-book of Practical organic chemistry including

qualitative organic analysis (Vogel) Third edition.

**********************************

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